The objectives of this research proposal are to investigate methods for the preparation of the epidithiopiperazinedione ring system as this relates to the synthesis of gliotoxin, sporidesmin, and related epidithiopiperazinedione antibiotics. The basic synthetic approach will involve preparation of appropriate alpha-mercapto-alpha--amino acids from alpha-acylaminoacrylic acids, and conversion thereof to epidithiopiperazinediones by initial formation of a disulfide bond and subsequent cyclization to the piperazine ring. Application will be made of the methods developed to synthesis of the natural antibiotics and related analogs.